COMMON ANCESTRY OF 3 ASHKENAZI-AMERICAN FAMILIES WITH ALPORT-SYNDROMEAND COL4A5 R1677Q

Mutations in the basement membrane collagen gene COL4A5 cause the prog ressive renal glomerular nephropathy and typical hearing loss that occ ur in X-linked Alport syndrome. Nearly all cases involve distinct muta tions, as expected for an X-linked disease that significantly reduces the fitness of affected males. A few exceptional COL4A5 mutations appe ar to be associated with a reduced disease severity and may account fo r a significant proportion of late-onset Alport syndrome in population s where a founder effect has occurred. The novel mutation reported her e, COL4A5 arg1677gln, has been detected in three independently ascerta ined Ashkenazi-American families, causes a relatively mild form of nep hritis with typical onset in the fourth or fifth decade, and may be in volved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews.